CN117286021A - Sample processing system, apparatus and method using semiconductor detection chip - Google Patents
Sample processing system, apparatus and method using semiconductor detection chip Download PDFInfo
- Publication number
- CN117286021A CN117286021A CN202311029375.6A CN202311029375A CN117286021A CN 117286021 A CN117286021 A CN 117286021A CN 202311029375 A CN202311029375 A CN 202311029375A CN 117286021 A CN117286021 A CN 117286021A
- Authority
- CN
- China
- Prior art keywords
- fluid
- sample
- chip
- adapter
- flow cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000012545 processing Methods 0.000 title claims abstract description 143
- 238000000034 method Methods 0.000 title claims abstract description 76
- 238000001514 detection method Methods 0.000 title claims abstract description 35
- 239000004065 semiconductor Substances 0.000 title abstract description 70
- 239000012530 fluid Substances 0.000 claims abstract description 492
- 238000010168 coupling process Methods 0.000 claims abstract description 74
- 238000005859 coupling reaction Methods 0.000 claims abstract description 74
- 230000008878 coupling Effects 0.000 claims abstract description 72
- 238000004458 analytical method Methods 0.000 claims abstract description 45
- 230000003321 amplification Effects 0.000 claims description 30
- 238000003199 nucleic acid amplification method Methods 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 27
- 230000008569 process Effects 0.000 claims description 26
- 239000000758 substrate Substances 0.000 claims description 24
- 238000004891 communication Methods 0.000 claims description 21
- 238000007789 sealing Methods 0.000 claims description 8
- 239000012528 membrane Substances 0.000 claims description 6
- 230000007246 mechanism Effects 0.000 claims description 5
- 238000003556 assay Methods 0.000 claims description 4
- 238000004886 process control Methods 0.000 claims description 4
- 230000008859 change Effects 0.000 claims description 3
- 238000005464 sample preparation method Methods 0.000 claims description 3
- 238000003825 pressing Methods 0.000 claims description 2
- 239000000523 sample Substances 0.000 description 438
- 210000004027 cell Anatomy 0.000 description 165
- 239000000463 material Substances 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 26
- 238000011282 treatment Methods 0.000 description 20
- 238000012360 testing method Methods 0.000 description 19
- 230000003287 optical effect Effects 0.000 description 18
- 239000013060 biological fluid Substances 0.000 description 13
- 238000003752 polymerase chain reaction Methods 0.000 description 13
- 239000012491 analyte Substances 0.000 description 12
- 150000007523 nucleic acids Chemical class 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 108020004707 nucleic acids Proteins 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 239000000853 adhesive Substances 0.000 description 10
- 230000001070 adhesive effect Effects 0.000 description 10
- 238000001914 filtration Methods 0.000 description 9
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 230000009977 dual effect Effects 0.000 description 8
- 229910052710 silicon Inorganic materials 0.000 description 8
- 239000010703 silicon Substances 0.000 description 8
- 238000003491 array Methods 0.000 description 7
- 239000004593 Epoxy Substances 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 238000009396 hybridization Methods 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 238000002032 lab-on-a-chip Methods 0.000 description 5
- 238000005382 thermal cycling Methods 0.000 description 5
- 238000011534 incubation Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- 239000012472 biological sample Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 230000002934 lysing effect Effects 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 238000012163 sequencing technique Methods 0.000 description 3
- 238000013459 approach Methods 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 238000012993 chemical processing Methods 0.000 description 2
- 238000013375 chromatographic separation Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920002492 poly(sulfone) Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 238000003672 processing method Methods 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 239000013464 silicone adhesive Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 238000009210 therapy by ultrasound Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 1
- 238000012351 Integrated analysis Methods 0.000 description 1
- 241000724291 Tobacco streak virus Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000000712 assembly Effects 0.000 description 1
- 238000000429 assembly Methods 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 239000013013 elastic material Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- -1 filtration Substances 0.000 description 1
- 238000007672 fourth generation sequencing Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011491 glass wool Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 239000006148 magnetic separator Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000012284 sample analysis method Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012995 silicone-based technology Methods 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000004227 thermal cracking Methods 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
- G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
- B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6844—Nucleic acid amplification reactions
- C12Q1/686—Polymerase chain reaction [PCR]
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/028—Modular arrangements
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/04—Exchange or ejection of cartridges, containers or reservoirs
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/06—Fluid handling related problems
- B01L2200/0689—Sealing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/06—Auxiliary integrated devices, integrated components
- B01L2300/0627—Sensor or part of a sensor is integrated
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/08—Geometry, shape and general structure
- B01L2300/0809—Geometry, shape and general structure rectangular shaped
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2300/00—Additional constructional details
- B01L2300/12—Specific details about materials
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2400/00—Moving or stopping fluids
- B01L2400/06—Valves, specific forms thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Analytical Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Clinical Laboratory Science (AREA)
- Dispersion Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Automatic Analysis And Handling Materials Therefor (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Analysing Materials By The Use Of Radiation (AREA)
Abstract
Provided herein are systems for processing fluid samples for analysis with semiconductor detection chips. Such a system may include a sample processing cartridge (100) couplable with a chip carrier device (200) configured for transporting a processed fluid sample from the sample cartridge. The chip-carrier device may include one or more fluid channels extending between fluid-tight couplings attachable to the transport ports of the sample processing cartridge. The chip carrier device may comprise a plurality of parts or adapters including a fluid sample part, a flow cell part and a chip carrier. Methods of preparing a fluid sample and transporting the fluid sample from the sample cartridge into a chip carrier device for analysis using a semiconductor detection chip carried within the chip carrier device are also provided.
Description
The present application is a divisional application of the application date 2019, 9, 20, 201980076476.4, and entitled "sample processing system, apparatus, and method using semiconductor detection chip".
Cross Reference to Related Applications
The present application claims priority from U.S. provisional application No. 62/734,079, filed on date 20 at 9 of 2018, which is incorporated herein by reference in its entirety.
The present application relates generally to the following applications: PCT application US2016/025748 entitled "Fluidic Bridge Device and Sample Processing Methods" filed in month 2016, 4; U.S. Pat. No. 6,374,684 entitled "Fluid Control and Processing System" issued 8/25/2000; us patent 8,048,386 entitled "Fluid Processing and Control" filed on 25 th month 2 of 2002; and U.S. application Ser. No. 2017/0023281 entitled "Thermal Control Device and Methods of Use" filed on day 2016, 7 and 22; each of the above-mentioned patent applications is incorporated by reference herein in its entirety for all purposes.
Technical Field
The present application relates generally to fluid handling and, more particularly, to an apparatus, system and method for processing samples and facilitating transportation of prepared samples for further processing with a semiconductor chip apparatus, particularly, a semiconductor test chip.
Background
In recent years, considerable development has been achieved in the use of semiconductor chips in performing fluid sample analysis (e.g., testing of clinical, biological, or environmental samples). One continuing challenge is the processing of fluid samples in preparation for analysis using semiconductor chips. Such processing of the fluid sample typically includes a series of processing steps, which may include chemical, optical, electrical, mechanical, thermal, or acoustic processing of the fluid sample. Whether incorporated into a desktop instrument, portable analyzer, disposable cartridge, or a combination thereof, such processing typically involves complex fluidic components and processing algorithms. Developing a robust fluid sample processing system can be extremely challenging and expensive.
Conventional methods for processing fluid samples typically involve a large number of manual operations, while more recent methods have sought to automate many of the processing steps and may involve the use of sample cartridges employing a series of regions or chambers, each configured for subjecting a fluid sample to a particular processing step. As the fluid sample sequentially flows from a region or chamber of a cartridge to a region or chamber of a subsequent cartridge, the fluid sample undergoes processing steps according to a particular protocol. However, such systems typically include integrated analysis devices and are generally not suitable for use with semiconductor chips. Standard methods of testing chips using semiconductors, such as "lab on a chip" devices, typically require quite complex, time consuming and expensive efforts, requiring the chip to be incorporated into a conventional chip package, and then into a much larger system that utilizes conventional fluid delivery devices to deliver fluid samples to the chip device. The fluid sample is typically prepared by one or more completely separate systems (typically involving manual interaction) and then aspirated into a fluid delivery system for supply to the chip package. These challenges associated with pre-test and post-test procedures often minimize the advantages and benefits of such "lab-on-a-chip" devices, and present a practical barrier to the widespread use and acceptance of "lab-on-a-chip" devices in diagnostic testing.
Thus, there is a need to develop an apparatus that performs a wide range of sample processing steps in a robust and consistent manner and is compatible for use with semiconductor chips. The following methods and apparatus are also needed: the method and apparatus allow for seamless integration with the prior art and improve efficiency and throughput in fluid sample processing and handling and overcome the challenges described above.
Disclosure of Invention
Devices, methods, and systems are provided that facilitate the processing of fluid samples and the transport of processed samples for analysis using semiconductor test chips (also referred to as "chips," "test chips," or "semiconductor chips"). In one aspect, such methods and systems utilize existing sample processing techniques to perform one or more processing steps, and then deliver the processed fluid sample to an interface with a semiconductor chip, and further process using the semiconductor chip. Such further processing typically includes analysis of the target analyte with a semiconductor detection chip. In some embodiments, the present application also provides an apparatus for any one of: when testing is performed with a semiconductor test chip, the chip is powered, communicated, programmed, or signal processed.
In one aspect, the device is configured for use with any of a number of different types of chips and allows for plug-and-play methods to be employed to utilize semiconductor test chips. For example, the device allows the system to be used as a platform to easily accept and utilize existing "lab-on-a-chip" devices in a more cost effective manner. It is understood that the device may be configured for use with any type of semiconductor detection chip, including but not limited to CMOS chips, ion Sensitive FET (ISFET) chips, bulk acoustic chips, non-bulk acoustic chips, piezoelectric acoustic chips, and aperture array sensor chips. In addition, the semiconductor test chip may be adapted for use in an open package in any of a number of JDEC standards, including but not limited to quad flat no-lead (QFN), dual in-line (dual in-line), and BGA arrays. Alternatively, the semiconductor test chip may be mounted directly onto the PCB as a chip-on-board component. In some embodiments, the semiconductor detection chip is used as a biosensor that combines a biosensing element with a physical or chemical transducer to selectively (and in some embodiments, quantitatively) detect the presence of a specific analyte in a fluid sample. In some embodiments, the chip provides an electrical or optical output signal in response to a physical, chemical or optical input signal. The apparatus may also include features for power, communication, signal integration, and data flow when performing tests with the test chip, and may include software to facilitate use of the chip within the system. The device may be further configured to facilitate testing using a chip device by utilizing various "on-board" features, or may be configured for use with various "on-board" or "off-board features," as described in further detail below.
In one aspect, the present application relates to a system for processing and analyzing a fluid sample using a sample cartridge and a chip carrier device coupled to the sample cartridge. Such a system may include: a sample cartridge configured to hold a biological sample, the sample cartridge comprising a plurality of process chambers fluidly interconnected by a movable valve body; a module for performing sample preparation, the module having a cartridge receiver adapted to receive and removably couple with a sample cartridge; and a chip-carrier device having a fluidic interface, the chip-carrier device configured for fluidic coupling with the sample cartridge. When carried within the chip carrier of the device, the fluidic interface is in fluid communication with the flow cell chamber of the device, which is in fluid communication with the semiconductor detection chip. The chip-carrier device includes an electrical interface configured to power a chip when the chip is supported within a carrier of the device. The electrical interface may also be configured to facilitate communication with the chip, as well as signal processing and programming.
In some embodiments, the chip carrier device may include various on-board chip features, such as any of those described herein. The chip carrier device comprises: fluid sample adapters, flow cell (flowcell) adapters, and chip carrier components. The fluid interface is configured for fluid coupling with the sample cartridge, the fluid interface being in fluid communication with the first set of ports of the fluid sample adapter via the fluid path. The flow cell adapter may be coupled with the fluid sample adapter, the flow cell adapter defining a flow cell chamber that is in fluid communication with the fluid sample adapter when coupled with the fluid sample adapter through one or more flow cell ports of the flow cell adapter. The chip carrier may be coupled to or integrated with the flow cell adapter and includes a carrier portion configured to support the semiconductor chip. The chip-carrier device may further include an electrical interface electrically coupled to the carrier portion to power the chip when the chip is supported within the chip carrier. Chip carrier devices may include any of a variety of "on-board" features, including filters, pre-PCR chambers, sonication chambers, valves/seats, thermal cycling chambers, magnetic separators, optical interrogation, optical links, RF, magnetic, or any feature or capability related to testing of chip devices.
In some embodiments, the device may be configured for use with various "in-board" features of the system, e.g., a chip carrier device may be engaged with an interface or separate device of the system configured to perform various functions, which may include, but is not limited to, components for sample processing, thermal cycling, communication, testing, signal processing, and the like. Such a system may include an electrical interface or various other components separate from but interfaced with the chip-carrier device.
In some embodiments, the chip-carrier device is configured for use with various "off-board" features, e.g., the chip-carrier device may facilitate delivery to an external device or interface, or facilitate delivery of a prepared fluid sample to a portion of a chip that interfaces with one or more external off-board components (e.g., thermal cycling, electrical interface, detection interface). In some embodiments, the device may be bridged or linked to a separate device or module for front-end detection devices, such as MALDI-TOF, mass spectrometer, NMRI, or other such detection devices.
In some embodiments, the sample cartridge employs a rotary valve configuration to control fluid movement within the cartridge, which allows selective fluid communication between the fluid sample processing region and the plurality of chambers in the cartridge. Non-limiting exemplary chambers can include sample chambers, reagent chambers, waste chambers, wash chambers, lysate chambers, amplification chambers, and reaction chambers. Fluid flow between the fluid sample processing region and each chamber is controlled by adjusting the position of the rotary valve. In this way, the metering and dispensing of fluids in the cartridge may be varied according to a particular protocol, which allows sample preparation to be adaptable to different protocols, such as may be associated with a particular sample type for different types of analysis or different types of samples. For example, the sample cartridge may include a device for cell lysis, e.g., an ultrasonic treatment device, so that bacteria and cells in the fluid sample to be analyzed may be lysed. Additional cracking methods suitable for use in the present application are well known to those skilled in the art and may include chemical, mechanical and thermal cracking. In some embodiments, the sample comprises a bacterium, eukaryotic cell, prokaryotic cell, or viral particle.
In some embodiments, the sample processing includes a sample processing step, an intermediate processing step, and a further processing step performed from the initial sample preparation step to facilitate detection of a target analyte in a biological sample with the semiconductor chip. For example, sample processing may include preliminary preparation steps such as filtering, grinding, shredding, concentrating, capturing fragments or purifying a crude sample, or steps for fragmenting DNA or RNA of a target analyte, such as by ultrasound or other mechanical or chemical methods. Sample processing may include various intermediate processing steps such as filtration, chromatography, or further processing of nucleic acids in the sample including, but not limited to, chromatography, bisulfite treatment, reverse transcription, amplification, hybridization, ligation, or fragmentation of DNA or RNA. Sample processing may further include final processing steps such as final amplification, hybridization, sequencing, chromatography, filtration, and mixing with reagents for detection of target analytes, which may include optical, chemical, and/or electrical detection. In some embodiments, the sample processing device is configured to perform initial and/or intermediate processing steps, while the semiconductor chip disposed within the device is configured to perform final processing, such as any of those described herein or known to those of skill in the art of target analyte detection. In some embodiments, the sample processing device is configured to perform at least a first step throughout sample processing and to deliver a fluid sample to the semiconductor chip to perform at least a subsequent step in the process, which may include detecting a target analyte. In another embodiment, the fluid sample may be transported from the semiconductor chip back to the sample processing device for additional processing. In some embodiments, to achieve additional new or enhanced functionality, one or more features may be included on the silicon chip that provide sample processing and/or sample preparation capabilities consistent with silicon-based technology. For example, the chip may include one or more features for finer fluidic manipulation, finer sample processing, or any compatible sample processing and/or preparation steps. Such techniques and functions may include, but are not limited to: separation based on electrophoresis; pumping fluid; and electrowetting-based fluid operations including droplet generation or pumping, flow sensors, etc. It should be understood that these chip features may be included in any of the embodiments described herein, and further that the chip carrier may be adapted for use with such chip features.
In some embodiments, the sample processing device may be a fluid control and processing system for controlling fluid flow between a plurality of chambers within a cartridge, the cartridge comprising a housing including a valve body having a fluid sample processing region that is continuously fluidly coupled with a fluid ejection chamber. The fluid discharge chamber is depressurized to draw fluid into the fluid discharge chamber and pressurizes to discharge fluid from the fluid discharge chamber. The fluid sample processing region includes a plurality of fluid delivery ports, each fluid delivery port being fluidly coupled to one of a plurality of external ports of the valve body. The fluid discharge chamber is fluidly coupled with at least one of the external ports. The valve body is adjustable relative to the plurality of chambers within the housing to allow the external port to be selectively placed in fluid communication with the plurality of chambers. In some embodiments, the valve body is adjustable relative to a housing having a plurality of chambers to place one external port in fluid communication with one of the chambers at a time.
In some embodiments of the cartridge, the fluid sample processing region may be disposed between the fluid ejection chamber and the at least one fluid delivery port. The term "fluid treatment zone" refers to a zone where a fluid sample is subjected to a treatment including, but not limited to, chemical treatment, optical treatment, electrical treatment, mechanical treatment, thermal treatment, or acoustic treatment. For example, the chemical treatment may include chemical processing, pH change, or enzymatic treatment; the optical treatment may include exposure to UV or IR light; the electrical treatment may include electroporation, electrophoresis or isoelectric focusing; mechanical treatments may include mixing, filtration, pressurization, grinding or cell disruption; the heat treatment may include heating or cooling from ambient temperature; and acoustic treatment may include the use of ultrasound (e.g., ultrasonic lysing). In some embodiments, the fluid treatment zone may include active components, such as filters, to facilitate treatment of the fluid. Non-limiting exemplary active components suitable for use in the present application include microfluidic chips, solid phase materials, filters or filter stacks, affinity matrices, magnetic separation matrices, size exclusion columns, capillaries, and the like. Suitable solid phase materials include, but are not limited to, beads, fibers, membranes, filter papers, lysing papers impregnated with lysing agents, glass wool, polymers or gels. In some embodiments, the fluid processing region is used to prepare a sample for further processing, for example, in a semiconductor chip device that is fluidly coupled to a fluid sample processing device. Other active elements suitable for use in the present application are well known to those skilled in the art. In some embodiments, the energy delivery member is operably coupled with the fluid sample processing region for delivering energy to the fluid sample processing region for processing fluid contained in the fluid sample processing region. In some embodiments, the valve body includes a crossover passage, and the valve body is adjustable relative to the plurality of chambers such that the crossover passage is in simultaneous fluid communication with two of the chambers. The cartridge housing includes one or more branches extending to one or more delivery ports to which the reaction vessel may be attached to facilitate delivery of fluid samples from the chambers of the cartridge into the reaction vessel. In some embodiments, the reaction vessel extends from the housing of the cartridge. These aspects may be further appreciated by reference to U.S. patent No. 8,048,386. It should be appreciated that in various embodiments, fluid may flow into or out of the delivery port in either direction, and fluid flow is not restricted in any particular direction. For example, in embodiments having a pair of delivery ports, air may be pumped into or out of one of the pair of delivery ports to facilitate flow of the fluid sample through the fluid delivery ports into the conduits of the reaction vessel.
In some embodiments, a chip carrier device includes a fluid sample adapter having a pair of fluid channels with substantially constant cross-sectional cavity areas from one another. The cross-sectional area of each of the fluid passages maintains a substantially constant size and shape between the respective fluid-tight couplings. In some embodiments, the pair of fluid channels are spaced apart and sized to be properly received within two corresponding delivery ports in the sample cartridge housing. In some embodiments, the fluid sample adapter may include a support web structure separating at least two channels. In some embodiments, the fluid sample adapter may be configured such that the volume of each of the at least two channels is not substantially different, while in other embodiments, the channels are configured to have substantially different volumes.
In some embodiments, one or more fluid channels of the fluid sample adapter include a chamber configured for an initial sample preparation step, such as initial filtration of debris from a fluid sample, initial mixing with reagents, and/or initial breaking of DNA of a target analyte, such as an ultrasonic treatment chamber or sharp edge suitable for breaking or breaking cells or DNA strands. In some embodiments, the one or more fluid channels include one or more regions that may be adapted to provide controlled flow of a fluid sample, such as may be used for transient storage or collection of a fluid sample. Such regions may also be used, for example, for mixing, pre-amplification, or to facilitate preparation or analysis of a fluid sample.
In some embodiments, the fluid sample adapter includes fluid-tight couplings, each defined as a stub sized to be received within one or more corresponding ports in the sample cartridge. The stub may be sized to be fluidly coupled by a friction fit within a corresponding port in a cartridge or cartridge housing inserted into the cartridge. In some embodiments, the fluid sample adapter includes a pair of fluid channels fed by two inlet stubs that are matingly received along a portion of the cartridge housing having two fluid delivery ports. In some embodiments, the fluid-tight coupling may include a luer-lock (leur-lock) connection, a friction fit connection, a screw type connection, a snap fit connection, or the like.
In some embodiments, the fluid sample adapter includes a flange from which the inlet stub extends, the flange being engageable with a retaining member of the sample cartridge to retain the fluid-tight coupling and position of the chip carrier device when coupled with the sample cartridge. The sample cartridge may further comprise a gasket surrounding the plurality of fluid delivery ports, the gasket being made of a formable material, such as an elastic material, such that when the inlet portion of the first end of the chip carrier device is fluidly coupled with the at least two fluid delivery ports, the gasket member engages the proximal facing surface of the flange to ensure a fluid tight coupling.
In some embodiments, the chip-carrier device may include one or more features for further processing the fluid sample during transport through the chip-carrier device. In some embodiments, the chip carrier device may comprise at least one processing region in fluid communication with at least one of the fluid channels, wherein the processing region is not a sample preparation chamber. In some embodiments, the chip carrier device includes a pre-amplification chamber and/or an amplification chamber for performing a polymerase chain reaction or other suitable nucleic acid amplification assay (NAAT). In some embodiments, the chip-carrier device includes a flow cell adapted to engage an active area of a semiconductor chip carried within the chip-carrier device. In one aspect, the flow cell adapter facilitates direct contact of the fluid sample with the active area of the chip. In some embodiments, at least a portion of the chip carrier device is at least partially translucent or transparent so as to allow confirmation by visual observation or optical monitoring that the fluid sample is passing through the fluid sample adapter. In some embodiments, the fluid sample adapter may include one or more features that may provide additional processing steps, for example, a chamber for chemical processing such as bisulfite treatment, a pre-amplification chamber or filter, or features that facilitate passage of a fluid sample through the fluid sample adapter, such as gas permeable vents or bubble traps.
In some embodiments, the chip-carrier device has a length and dimensions large enough that when coupled with a sample cartridge mounted within a cartridge receiver of a sample cartridge processing module having a channel, the carrier extends to an instrument interface including an electrode contact array that interfaces with corresponding electrode contacts of an electrical interface board of the chip-carrier device to facilitate operation of a semiconductor chip through the instrument interface.
In some embodiments, the chip carrier device is defined by one or more components formed by a planar frame supporting and defining one or more fluid channels. Each of the planar frames may be formed of a sufficiently rigid material, typically a polymer-based material, to support one or more fluid channels such that the chip carrier device extends laterally from the sample cartridge into engagement with the instrument interface. In some embodiments, one or more of the planar frames is sufficiently rigid to withstand normal forces to the planar frame from electrical contacts of the instrument interface when engaged against an electrical interface board of the chip carrier device. Typically, the electrical contacts of the instrument interface are pogo pins that resiliently engage electrical contact pads of the interface of the chip carrier device when the instrument interface board is engaged with the chip carrier device. In some embodiments, the instrument interface board is configured to move or pivot toward the chip-carrier device so as to securely engage the corresponding electrical contacts when a sample cartridge coupled to the chip-carrier device is housed within the module. In other embodiments, the electrical contacts may be configured as edge connectors. It will be appreciated that the electrical contacts may be configured to connect by any suitable means or to accommodate any connection standard or means.
Another aspect of the present application provides methods of processing and analyzing samples using the chip carrier devices provided herein. Such a method may comprise the steps of: receiving a sample cartridge at a cartridge receiver of the module, the sample cartridge comprising a plurality of process chambers fluidically interconnected by one or more mechanisms; receiving an electronic instruction to process an unprepared sample into a prepared sample from a process control unit of the cassette receiver; performing a sample preparation method to process an unprepared sample into a prepared sample; and moving the prepared sample fluid into a chip carrier device that is fluidly coupled to the sample cartridge. The method may further comprise: analysis of the fluid sample is performed by a process control unit of a cartridge process module, using active elements of a chip supported within the chip carrier device, wherein the cartridge process module is electrically coupled to the chip through an instrument interface of the module.
Another aspect of the present application provides a method of transporting a fluid sample between a sample processing device, such as a sample cartridge, and a semiconductor chip provided herein. A non-limiting exemplary method includes: the sample processing device is fluidly coupled to the semiconductor chip via a chip carrier device carrying the semiconductor chip, the chip carrier device being fluidly coupled to the sample cartridge via one or more fluid ports. In some embodiments, the chip carrier device is configured to utilize one or more fluid ports on a sample processing device (e.g., a sample cartridge) to allow sample processing in the sample processing device (e.g., sample preparation) prior to delivering a processed fluid sample into the chip carrier device via the one or more fluid ports for subsequent processing (e.g., analysis) with the semiconductor chip of the carrier. In some embodiments, the method further comprises: the semiconductor chip is controlled by means of an instrument interface of the module in which the sample cartridge is accommodated. In some embodiments, the method further comprises: the chips in the carrier are controlled by a control module separate from the module, for example from outside the module or by a part of the additional module which is joined to the semiconductor chip via an access channel of the module. In some embodiments, fluid flow through one or more channels may be achieved by pressurizing/depressurizing or transferring a fluid sample through a sample processing device. Typically, instructions for transporting a fluid sample from a cartridge into a chip carrier device are provided by a control unit of a module that receives the sample cartridge and controls sample preparation therein. It will be appreciated that a variety of alternative configurations may be used to provide motive force for transporting the fluid sample through the chip carrier device, with the module passing through the fluid sample cartridge.
In some embodiments, a method for processing an unprepared sample may comprise the steps of: receiving a sample cartridge in a cartridge receiver of the module, the sample cartridge comprising a biological fluid sample to be analyzed, a plurality of process chambers fluidly interconnected by a movable valve body; receiving electronic instructions from the module to process the biological sample into a prepared sample; performing a sample preparation method in a sample cartridge to process a biological fluid sample into a prepared sample; delivering the prepared sample to a chip carrier device in fluid communication with the sample cartridge; and performing an analysis of the biological fluid sample by a chip carried within the chip carrier. In some embodiments, delivering the sample may include the steps of: moving the cartridge interface unit to move the valve body to change the fluidic interconnection between the plurality of sample processing chambers; applying pressure to the pressure interface unit according to the position of the valve body to cause fluid to flow between the plurality of process chambers; the prepared sample fluid is moved into a chip carrier device. Performing an analysis of the fluid sample may include: the operation of the chip is controlled by the module via an instrument interface board electrically coupled to the electrical interface board of the chip carrier device. The module may obtain any result of the analysis via the electrical interface and communicate the result to various other devices as needed.
Drawings
Fig. 1 is a diagrammatic view of a sample cartridge fluidly coupled to an instrument interface plate and a chip carrier device associated with a module for receiving and operating the sample cartridge in accordance with some embodiments of the present application.
Fig. 2A illustrates an instrument interface board of a module having an array of electrical contacts for connection with electrical contact pads of a chip carrier device when a sample cartridge is housed within the module, as shown in fig. 2B, according to some embodiments.
Fig. 3 illustrates a detailed view of a sample cartridge fluidly coupled to a chip carrier device according to some embodiments.
Fig. 4A-4C illustrate various views of a fluid sample adapter component of a chip carrier device according to some embodiments.
Fig. 5A-5C illustrate various views of a chip-carrier component of a chip-carrier device according to some embodiments.
Fig. 6A and 6B illustrate detailed and cross-sectional views of an assembled chip carrier device according to some embodiments.
Fig. 7A and 7B illustrate detailed views of an assembled chip carrier device according to some embodiments.
Fig. 8 and 9 illustrate a fluid sample adapter component coupled with a sample cartridge and an assembled chip carrier device, respectively, according to some embodiments.
Fig. 10 illustrates an alternative chip-carrier device coupled to a sample cartridge, including a fluid sample adapter, a flow cell adapter, and a chip-carrier component, according to some embodiments.
Fig. 11A-11C illustrate various views of a fluid sample adapter component of a chip carrier device according to some embodiments.
Fig. 12A-12C illustrate various views of a flow cell adapter component of a chip carrier device according to some embodiments.
Fig. 13A-13C illustrate various views of a chip-carrier component of a chip-carrier device according to some embodiments.
Fig. 14A-14B illustrate a chip carrier component coupled with a flow cell adapter component according to some embodiments.
Fig. 15A-15C illustrate various views of an assembled chip carrier device according to some embodiments.
Fig. 16 illustrates a sample cartridge coupled with a fluid sample adapter component of a chip carrier device, and fig. 17 illustrates an assembled chip carrier device coupled with a sample cartridge, according to some embodiments.
Fig. 18 illustrates an alternative embodiment employing different detection modes, each configured for use with a sample cartridge, according to some embodiments.
Fig. 19-20 illustrate methods of processing a sample through a semiconductor chip using sample processing in a sample cartridge according to some embodiments.
Detailed Description
The present application relates generally to a system, device and method for fluid sample processing and analysis, and in particular, to a system, device and method for transporting a fluid sample from a sample processing device into a chip carrier device for analysis using a semiconductor chip.
I. Exemplary System overview
In one aspect, the present application relates to a chip-carrier device having one or more fluid conduits fluidly couplable with one or more ports of a sample cartridge to facilitate transport of a processed fluid sample from the cartridge through the one or more fluid conduits into the chip-carrier device for further processing by a semiconductor chip in the chip-carrier device. In some embodiments, the sample cartridge is received by a module that facilitates manipulation of the sample cartridge to perform processing of the fluid sample and delivery of the processed fluid sample into the chip-carrier device, and the module further includes an instrument interface that is electrically coupled to the chip-carrier device to facilitate operation of the semiconductor chips carried within the device.
In some embodiments, the chip-carrier device may include various features, such as one or more specific regions, each region being adapted for a sample processing procedure or a sample analysis procedure. Non-limiting exemplary sample processing procedures can include filtration, concentration, incubation, mechanical, electrical, optical, chemical treatment, and/or amplification. In some embodiments, the chip carrier device includes a pre-amplification region for performing polymerase chain reaction or other types of nucleic acid amplification procedures known to those of skill in the art. Other sample processing procedures suitable for use in the present application are well known to those skilled in the art. Non-limiting exemplary sample analysis procedures can include amplification, hybridization, optical interrogation, isoelectric focusing, antibody binding and detection (e.g., ELISA), sequencing, chromatography, and lateral flow chromatography. Other sample analysis methods suitable for use in the present application are well known to those skilled in the art. The chip carrier device may also include one or more features including filters, wells, membranes, ports, and windows to allow additional processing steps to be performed during the delivery of the fluid sample to the semiconductor chip.
A. Sample box device
The sample cartridge device may be any device configured to perform one or more processing steps related to the preparation and/or analysis of a biological fluid sample according to any of the methods described herein. In some embodiments, the sample cartridge device is configured to perform at least sample preparation. The sample cartridge may also be configured to perform additional processes, such as detecting a target nucleic acid in a Nucleic Acid Amplification Test (NAAT), e.g., a Polymerase Chain Reaction (PCR) analysis, by using a reaction tube attached to the sample cartridge. The preparation of a fluid sample typically includes a series of processing steps, which may include chemical, electrical, mechanical, thermal, optical, or acoustical processing steps according to a particular protocol. Such steps may be used to perform various sample preparation functions, such as cell capture, cell lysis, binding of analytes, and binding of unwanted materials.
A sample cartridge suitable for use with the present application includes one or more delivery ports through which prepared fluid samples can be delivered to a reaction tube for analysis. Fig. 1 illustrates an exemplary sample cartridge 100 suitable for use with a chip carrier device according to some embodiments. Typically, such a sample cartridge is associated with a reaction tube 110 (see embodiment 0 in fig. 18), the reaction tube 110 being adapted to analyze a fluid sample processed within the sample cartridge 100. Such a sample cartridge 100 includes various components including a main housing having one or more chambers for processing a fluid sample, which typically includes preparing the sample prior to analysis. According to its conventional use, after assembly of the sample cartridge 100 and the reaction tube 110 (as shown in fig. 18), a biological fluid sample is deposited within the chambers of the sample cartridge and the cartridge is inserted into a cartridge processing module configured for sample preparation and analysis. The cartridge processing module then facilitates the processing steps required for sample preparation and delivers the prepared sample through one of a pair of delivery ports into the fluid conduit of the reaction tube 110 attached to the housing of the sample cartridge 100. The prepared biological fluid sample is then transferred to the chamber of the reaction tube 110, where the biological fluid sample can be subjected to nucleic acid amplification. In some embodiments, the amplification is a polymerase chain reaction. In some embodiments, the excitation means and the optical detection means of the module are used to detect optical emissions indicative of the presence or absence of a target nucleic acid analyte of interest, such as a bacteria, virus, pathogen, toxin or other target analyte, simultaneously with the amplification of the biological fluid sample. It should be appreciated that such a reaction tube may include a variety of different chambers, conduits, or microwell arrays for detecting target analytes. The sample cartridge may be provided with means for performing preparation of a biological fluid sample prior to delivery into the chip carrier device. Any chemical reagents required for viral or cellular lysis, or means for binding an analyte of interest (e.g., a reagent bead), may be contained within one or more chambers of the sample cartridge and thus may be used for sample preparation.
An exemplary use of a reaction tube for analyzing a biological fluid sample is described in commonly assigned U.S. patent application No. 6,818,185, entitled "Cartridge for Conducting a Chemical Reactions," filed 5/30/2000, the entire contents of which are incorporated herein by reference for all purposes. Examples of sample cartridges and related modules are shown and described in U.S. patent No. 6,374,684 entitled "Fluid Control and Processing System" filed 8/25/2000 and U.S. patent No. 8,048,386 entitled "Fluid Processing and Control" filed 2/2002, the entire contents of which are incorporated herein by reference, and which are incorporated herein by reference in their entirety.
Various aspects of the sample cartridge 100 shown in fig. 3-17 may be further understood by reference to U.S. patent No. 6,374,684, which describes certain aspects of the sample cartridge in more detail. Such a cartridge may include a fluid control mechanism, such as a rotary fluid control valve, connected to the chambers of the cartridge. The rotation of the rotary fluid control valve allows fluid communication between the chambers and the valve to control the flow of the biological fluid sample deposited in the cartridge into the different chambers where the various reagents may be provided according to the particular protocol required to prepare the biological fluid sample for analysis. To operate the rotary valve, the cartridge processing module includes a motor, such as a stepper motor, which is typically coupled to a drive train that engages features of the valve in the sample cartridge to control movement of the valve and the resulting movement of the fluid sample according to a desired sample preparation protocol. The fluid metering and dispensing function of rotary valves according to a particular sample preparation protocol is set forth in U.S. patent No. 6,374,684, which is incorporated herein for all purposes.
It should be appreciated that the above-described sample processing cartridge is only one example of a sample processing device suitable for use with a chip carrier device according to embodiments described herein. While a chip carrier structure that allows for the use of such sample processing cartridges is particularly advantageous as it allows for the use of conventional fluid sample cartridges, it should be understood that the concepts described herein may be applied to a variety of other sample processing devices, which may include a variety of other sample cartridge structures or other fluid sample processing devices and components.
B. Chip carrier device
The chip carrier device is adapted to fluidly couple the semiconductor chip to the sample cartridge described herein. In some embodiments, the chip carrier device comprises an electrical interface adapted to engage with an instrument interface board of a sample processing module that operates the sample processing cartridge. It is understood that the chip-carrier device may be configured for use with any type of chip, including but not limited to CMOS chips, ISFET chips, bulk acoustic chips, non-bulk acoustic chips, piezoelectric acoustic chips, and aperture array sensor chips. In addition, the chip may be adapted for use in any of a number of JDEC standards used in open packages, including but not limited to QFN, dual in-line (dual in-line), and BGA arrays. Alternatively, the chip may be mounted directly onto the PCB as a chip-on-board assembly. In some embodiments, the chip-carrier device is designed to allow electrical manipulation of the chip through the instrument interface of the module, through which the biological fluid sample is analyzed. This is achieved by means of electrical contact pads of the chip-carrier device, which are electrically coupled to the chip and engage with the instrument interface of the module.
The arrangement described above allows for a more seamless transition between processing a fluid sample with a sample cartridge and subsequently processing or analyzing the fluid sample with a chip in a chip carrier device. This configuration facilitates the industrial development of semiconductor chip devices by standardizing the processing or preparation of samples and delivering processed samples to the chip devices. The preparation of samples can be a time-consuming and laborious process performed by hand, and can be challenging to develop in next generation chip devices. By replacing the reaction tube with a chip carrier device, a user can prepare a sample in a sample cartridge using the sample cartridge, and then transport the prepared sample into an attached chip carrier device for analysis by a semiconductor chip carried in the chip carrier device. This configuration accelerates the development of semiconductor chips by utilizing existing sample preparation processes configured for PCR detection and allowing such processes to be used with semiconductor chip devices.
In some embodiments, the chip carrier device may include one or more processing features in fluid communication with one or more of the fluid flow channels, such as one or more chambers, filters, collectors, membranes, ports, and windows, to allow additional processing steps to be performed during the transfer of the fluid sample to the second sample processing device. Such chambers may be configured for use with amplification chambers for nucleic acid amplification, filtration, chromatography, hybridization, incubation, chemical treatment, such as bisulfite treatment, and the like. In some embodiments, the chamber allows for a substantial portion, if not the entire fluid sample to accumulate, for further processing or analysis as desired for a particular protocol. In some embodiments, the chamber includes an at least partially transparent window that allows for optical detection of an analyte of interest in the fluid sample passing through the chamber during transport of the fluid sample through the chip carrier device. This feature is particularly advantageous when screening for the presence or absence of multiple analytes, or analysis may require several or redundant detection steps or require further processing and/or analysis of the fluid sample after detection of a particular target or analyte of interest.
C. Instrument interface
The instrument interface of the module is a circuit board adapted to engage the electrical interface of the chip carrier device to allow the module to electrically control the semiconductor chip. In some embodiments, the instrument interface is located within a common housing of the module, thereby providing a more seamless process between the fluid sample cartridge and the chip carrier device. The instrument interface may be controlled by the module in conjunction with the transport of the fluid sample from the sample cartridge to the semiconductor chip.
In some embodiments, the instrument interface board is mechanically mounted on a pivot that moves toward the chip carrier device when housed within the module. The instrument interface board is configured to pivot from an open position prior to loading the sample cartridge to an engaged position upon loading. A cam (not shown) positions the interface board in contact with an electrical interface board on the chip carrier device. Spring pins on the instrument interface board contact electrical contact pads on the electrical interface board to allow the module to control analysis of the fluid sample by a chip carried within the chip carrier device.
In some embodiments, the chip-carrier device is configured with fluid flow channels having similar flow dimensions as the fluid channels described above with reaction tubes 110 (see U.S. Pat. No. 6,374,684). This allows the same mechanism that is used to transport the fluid sample through the reaction tube to the chip carrier device. Those of skill in the art will appreciate that the fluid sample may be delivered to the chip carrier device in any number of ways in accordance with various other aspects of the present application described herein.
Exemplary chip carrier devices and related systems
A. Overview of the System
Fig. 1 shows an overview of a system utilizing a conventional fluid sample cartridge 100 fluidly coupled to a chip carrier device 200. The fluid sample cartridge 100 is adapted to be inserted into a compartment of a processing module configured to perform one or more processing steps on a fluid sample contained within the fluid sample cartridge by manipulating the fluid sample cartridge. The instrument interface 300 of the module is incorporated into the module within the compartment housing the cartridge 100 and includes a plate 301 having a socket opening 302 through which the chip carrier device 200 extends when the cartridge 100 is positioned within the compartment. The instrument interface 300 further includes an instrument board 310, such as a PCB board, extending along the major planar surface of the chip-carrier device 200, and including electrical contacts 312, the electrical contacts 312 being arranged to electrically couple with corresponding contact pads on the major planar surface of the chip-carrier device.
Fig. 2A shows an instrument interface board 310 of the module and electrical contacts 312 for engaging electrical contact pads of the chip carrier device. Typically, contacts 312 are arranged in a pattern, such as a rectangular array, corresponding to contacts of the chip carrier device. In one aspect, the electrical contacts are configured to facilitate on-board electrical connection. In this embodiment, contacts 312 are configured as pogo pins to deflect when chip-carrier device 200 is inserted through socket opening 302, thereby providing a reliable electrical coupling between contacts 312 and corresponding contacts on chip-carrier 230 of chip-carrier device 200, as shown in fig. 2B. Although a rectangular array of pogo pins is described herein, it is understood that electrical contacts may be arranged in various other patterns and various other contact structures may be implemented, depending on the respective chip carrier device. In some embodiments, the electrical contacts may be configured as one or more edge connectors or other types of multi-pin connector arrangements. It will also be appreciated that the instrument interface need not utilize each contact as needed for compatible use with carriers having a different number or arrangement of contact pads. In some embodiments, the electrical contacts may include additional adapters to be suitable for use with a variety of different types of chip-carrier devices. In some embodiments, the semiconductor controller is packaged as an attachment to the chip carrier such that minimizing signal connectivity may be cost effective. This approach may use any suitable connector device, which may include standard connector types, such as USB interfaces (e.g., [ +1, -2, sig 3, sig 4 ]).
A. Fluid sample adapter
Fig. 3 illustrates a detailed view of sample cartridge 100 fluidly coupled to chip-carrier device 200, according to some embodiments. In this embodiment, chip carrier device 200 includes a fluid sample adapter 201, with fluid sample adapter 201 having a fluid flow portion on one side and a flow cell portion on the opposite side. As can be further appreciated by reference to fig. 14A-14B, fluid sample adapter 201 is fluidly coupled to sample cartridge 100 by fluid interface 211, fluid interface 211 having a pair of fluid ports 212, 214 coupled with corresponding fluid ports of the sample cartridge. On one side, the fluid sample adapter 201 includes a fluid flow portion 210 defined therein, as shown in fig. 4A, while on the opposite side, the fluid sample adapter has a flow cell portion 220 defined therein, as shown in fig. 4B. The flow cell portion 220 is fluidly coupled to the fluid flow portion 210 such that fluid introduced through the fluid inlet of the fluid interface 211 flows through the fluid flow portion 210 before flowing into a flow cell 224 defined in the flow cell portion 220. Flow cell portion 220 is configured to couple with chip carrier portion 230 such that a chip carried within chip carrier portion 230 engages flow cell chamber 224. Flow cell portion 220 may include one or more coupling features 229 (e.g., six protruding knobs around the perimeter of the major face) to facilitate alignment and secure coupling of chip carrier portion 230 with fluid sample adapter 201. Any or all of the adapter or flow cell portions of the chip carrier device are formed of a suitably rigid material such that chip carrier device 200 extends outwardly from sample cartridge 100. In some embodiments, chip-carrier device 200 is supported only by a pair of inlet studs of the fluid interface of fluid sample adapter 201, which are appropriately received within a corresponding pair of fluid ports and surrounding flange of sample cartridge 100.
B. Fluid flow portion
Fig. 4A-4C depict an exemplary fluid sample adapter device according to some embodiments. As shown in fig. 4A, the fluid sample adapter portion 210 includes two fluid channels or conduits that are spaced apart and extend within the chip carrier device. The channels are separated and supported by a support web structure. The chip carrier device may be made of any material suitable for delivering the selected fluid sample so as not to interfere with processing or analysis of the sample, and generally inert plastic or polymer-based materials may be used. In some embodiments, the components of the chip carrier are formed of polycarbonate, polysulfone, or any suitable material (e.g., any material compatible with the adhesive). In some embodiments, the material is compatible with a silicone adhesive. In some embodiments, the material used to fabricate the chip carrier device is a transparent or partially translucent material to allow for sample transport and/or optical detection/monitoring of the fluid channel by visual inspection of the material.
In some embodiments, the chip carrier device includes a fluid sample adapter configured with the same Luer (Luer) port and flange arrangement of a fluid interface as a typical PCR reaction tube, so that the fluid sample adapter can be easily engaged with a sample cartridge. The fluid sample adapter is configured such that the port is fluidly connected to an optional PCR pre-amplification chamber. Alternatively, the amplification chamber may house filters, affinity matrices, magnetic capture zones, or other active areas that can be manipulated by the module. Typically, the fluid channel is defined in a first substrate and sealed by a second substrate, such as a membrane, similar to the structure of a conventional PCR reaction tube. In some embodiments, the fluid sample adapter is further characterized by alignment and assembly bosses and mechanical snaps such that the chip carrier component or chip can be easily secured to the flow cell of the flow cell portion.
In some embodiments, the fluid sample adapter has a length of about 12cm, 11cm, 10cm, 9cm, 8cm, 7cm, 6cm, 5cm, 4cm, 3cm, 2cm, or 1cm. In some embodiments, the length of the fluid sample adapter 210 is between 3cm and 5cm, for example about 4cm, from the flange of the fluid interface 211, and the fluid channels extend in parallel and are spaced about 1cm apart. This configuration allows for a substantially fluid tight connection having substantially the same structure as a conventional reaction tube. The fluid-tight coupling of each channel is defined by a stub, each stub being sized to be received in a respective external port of the sample cartridge to facilitate fluid-tight coupling of the fluid channel with a respective fluid channel of the chip-carrier device. For example, the stubs at the fluid interface 211 at the proximal end of the chip carrier device 200 along the fluid inlet and outlet 212, 214 act as inlet stubs for the prepared fluid sample to flow in through the fluid path of the fluid flow section 210. In some embodiments, the stubs may have an outer diameter of between 2mm-10mm, for example, the outer diameter may be 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, or 10mm. Typically, the stub has an outer diameter of about 3mm and extends from the flange a distance of about 2mm-5mm, for example about 3mm, to facilitate fluid-tight coupling. In some embodiments, the inner diameter of each of the one or more channels within any component of the chip carrier device may be in the range of 1mm to 5 mm.
In some embodiments, the fluid sample adapter 201 includes one or more channels extending between the fluid-tight couplings without any chambers, valves, or ports between the proximal and distal ends. In some embodiments, the fluid sample adapter 201 includes one or more valves or ports. In some embodiments, the one or more channels may include one or more chambers or regions that may be used to process or analyze a fluid sample. For example, the fluid sample adapter may include one or more chambers or regions for thermal amplification of a nucleic acid target in a sample, filtration of a sample, chromatographic separation of a sample, hybridization, and/or incubation of a sample with one or more assay reagents.
While the fluid-tight coupling shown in fig. 4A includes a stub extending from the flange of the fluid interface 210, it should be appreciated that various other fluid-tight couplings suitable for fluid-coupling with other types of devices may be designed as desired. Non-limiting exemplary fluid-type couplings suitable for use with the present application include luer lock connections, snap fit connections, friction fittings, snap fit connections, and threaded connections. Other types of fluid tight couplings suitable for use in the present application are known to those skilled in the art.
As can be seen in fig. 4A-4C, the fluid sample adapter 201 is defined by one or more planar substrates defining a fluid path 213 coupled to a fluid interface 211. Fluidic interface 211 is a structural member from which a majority of the planar frame is cantilevered when fluidic interface 211 is coupled to the sample cartridge. The fluid interface 211 may be integrally formed with the planar frame. Fluidic interface 211 also serves as a mechanical coupling to sample cartridge 100. Fluidic interface 211 includes a fluid inlet 212 and a fluid outlet 214 that provides a fluidic interface to the sample cartridge device. Each of the fluid inlet 212 and the fluid outlet 214 is fluidly coupled to a fluid path 213 formed in the planar substrate. It is understood that fluid sample adapter 210 and fluid interface 211 may be integrally formed as a single component.
In some embodiments, the fluid path 213 is defined primarily along one major face of a planar substrate and is surrounded by a second planar substrate, such as a film heat sealed to the substrate, so as to enclose the channels and chambers defined within the substrate. The fluid path 213 leads to a flow cell interface extending in a width direction through a set of flow cell ports 226, 228 of the fluid sample adapter 201 into the flow cell 224, the set of flow cell ports being defined in the flow cell adapter portion 220, the flow cell adapter portion 220 being defined on opposite sides of the fluid sample adapter 201. In this embodiment, the flow cell interface includes an inlet flow cell port 228 and an outlet flow cell port 226, the inlet flow cell port 228 and the outlet flow cell port 226 allowing for controlled delivery of fluid into the flow cell chamber 224 through the fluid sample adapter 201 via the fluid inlet 212 and the fluid outlet 214. Typically, when the fluid sample adapter 201 is oriented vertically, the flow cell inlet 228 is disposed below the flow cell outlet 226 to facilitate controlled fluid flow through the flow cell chamber 224. In this embodiment, a fluid channel is defined along one major face of the fluid sample adapter 201 and a flow cell portion is defined within the opposite major face. In this embodiment, these portions are formed as an integrally formed component. However, it is understood that the fluid sample adapter may be formed from one or more components.
It should be understood that the use of the terms "inlet" and "outlet" does not limit the function of any of the fluid inlets or outlets described herein. Fluid may be introduced and withdrawn from either or both. In some embodiments, the fluid path 213 is valveless, such that an external increase or decrease in pressure may be applied by an external system via the fluid inlet 212 and the fluid outlet 214 to move fluid within the fluid path 213, the fluid path 213 extending from the fluid inlet 212 to the fluid outlet 214. The fluid path 213 may be circular or rectangular in cross-section and may have a diameter or width ranging from about 50 μm to about 2 mm. Typically, the diameter or width is in the range of about 250 μm to about 1 mm. In this embodiment, fluid path 213 includes a chamber 215 that is an enlarged portion of fluid path 213 between flow cell chamber 224 and fluid inlet 212 that is sized to accommodate most or all of the fluid sample delivered from the sample cartridge to facilitate various processes, including but not limited to flow metering, mixing, pre-amplification, thermal cycling, or any other desired sample processing. It will be appreciated that various other components may be incorporated into the fluid sample adapter, such as valves, filters, windows, or any other desired feature.
In some embodiments, the chip-carrier device (or at least part of the component) is arranged to be pre-attached to the sample cartridge, wherein the fluid-tight couplings are coupled with the respective fluid ports of the cartridge. For example, a sample cartridge that has been coupled to fluid sample adapter 201 may be provided so that an end user may insert any chip into chip carrier 230 components and couple into flow cell portion 220 to facilitate sample detection with the chip.
C. Flow cell portion
The flow cell portion of the fluid sample adapter 201 is configured with an open chamber that forms a closed flow cell chamber when engaged with the active area of the chip within the chip carrier to facilitate analysis of the fluid sample with the chip. The flow cell is shaped and configured to be fluidly coupled with a chip within a chip carrier attached to the fluid sample adapter 201. Typically, the fluid channels of the fluid flow section are fluidly connected to the flow cell chamber by fluid ports 226, 228 at the top and bottom of the flow cell chamber. The chamber is formed by raised bosses or ridges that contact the active silicon or glass elements used in the detection scheme. The active element is located on a chip carried within a chip carrier and secured to the flow cell by bonding and sealing, which may be accomplished by a variety of means (e.g., using an epoxy preform, dispensed epoxy or other adhesive, a gasket with adhesive, mechanical features, or a variety of other means). The purpose of the flow cell adapter is to create a complete flow cell chamber defined by the detection surface on one side and by the flow cell dispenser on the remaining side. Flow cell portion 220 also includes one or more coupling features 229, defined as alignment and assembly bosses and mechanical snaps, which are received in corresponding holes 239 of chip carrier 230 to align and securely couple chip carrier 230 and flow cell portion 220, as shown in cross-section A-A in fig. 4C.
Fig. 4B shows a detailed view of an exemplary flow cell portion 220 for use with chip device 200. In this embodiment, the flow cell adaptor 220 is configured to be in fluid communication with the fluid flow portion 210 shown in fig. 4A. As shown in fig. 4B, the flow cell portion may be formed within a planar substrate formed of a rigid material (e.g., a polymer or any suitable material) to define an open flow cell chamber 224, and flow cell ports 226, 228. Flow cell portion 220 is further configured to couple with a chip carrier to form a closed flow cell chamber through an active area of a chip carried therein. Top flow cell port 226 and bottom flow cell port 228 fluidly couple the flow cell chamber with the fluid channels of the fluid flow portion to allow for controlled flow of fluid sample into or out of the flow cell chamber when the inlet and outlet ports 212, 214 of chip-carrier device 200, which are fluidly coupled to sample cartridge 100, are under controlled pressurization.
D. Chip carrier
Fig. 5A-5C illustrate detailed views of chip carrier 230 of a chip carrier device according to some embodiments. As can be seen in fig. 5A, the chip carrier 230 is defined within a substantially planar substrate 231, the substrate 231 including a contoured region 236, the contoured region 236 being sized to accommodate a chip and configured to have a plurality of electrical contacts 234, the electrical contacts 234 being arranged to electrically couple with corresponding contacts of the chip when the chip is accommodated therein. In this embodiment, the contoured region 236 is square, and the electrical contacts 234 are configured to receive and couple with a chip, as shown in fig. 5A. The contoured region 236 includes raised ridges along its perimeter to engage corresponding portions of the flow cell portion and effectively seal the chip within the chip carrier device. The raised boss or ridge surrounding the open flow cell chamber engages the active surface of the chip to form a closed flow cell chamber, as described above.
The electrical contacts 23 are electrically coupled with corresponding contact arrays 232 of an electrical interface board disposed on an opposite side of the chip carrier 230, as shown in fig. 5B. The contact array 232 is defined as an array of enlarged contact pads arranged to facilitate contact with corresponding electrical contacts of the module's instrument interface 300, typically pogo pins. Fig. 5C shows a cross-sectional view of chip carrier 230, wherein the chip is carried and electrically coupled within socket 236. Wire bonding is not shown in this view. The electrical interface board may also be provided with passive and active electronic components in addition to those of the chip carrier, as required for various other tasks. For example, such components may include any components required for signal integrity, amplification, multiplexing, or other such tasks.
E. Chip
In some embodiments, if chip 240 includes a silicon sensor element, it may be bonded within chip carrier 230 and wire bonding applied to electrically couple the silicon element to chip carrier 230. In other embodiments, the chip may simply be pressed into the recess such that the friction fit provides sufficient electrical contact between the respective contacts.
In some embodiments, chip 240 is a semiconductor diagnostic chip. In some embodiments, the semiconductor diagnostic chip is configured to perform sequencing of the nucleic acid target molecules by nanopore sequencing, which detects changes in conductivity, and does not require optical excitation or detection. The underlying technology of such chips can be further understood by reference to U.S. patent No. 8,986,928. In some embodiments, the semiconductor diagnostic chip analyzes the sample for other properties of the target molecule, such as molecular weight and similar characteristics. Such techniques can be achieved by reference to the Xiaoyun Ding, et al surface active wave microfluidics, lab chip 2013 ep 21;13 (18) 3626-3649, etc. In some cases In an embodiment, the semiconductor diagnostic chip uses surface plasmon resonance to provide target molecule analysis, e.g., biocore as provided at GE Healthcare UK Limited TM As used in the system and as described in its Biocore Sensor System Handbook (see gelifesciences. Com/Biacore). The entire contents of each of the above references are incorporated herein by reference in their entirety. While semiconductor diagnostic chips are preferred, it should be understood that the concepts described herein are applicable to any type of chip suitable for performing processing or analysis of fluid samples.
It is understood that the chip carrier device may be configured for use with any type of semiconductor chip including, but not limited to, CMOS chips, ISFET chips, bulk acoustic chips, non-bulk acoustic chips, piezoelectric acoustic chips, and aperture array sensor chips. In addition, the chip may be adapted for use in any of a number of JDEC standards used in open packages, including but not limited to QFN, dual in-line (dual in-line), and BGA arrays. Alternatively, the chip may be mounted directly to the PCB as a chip-on-board assembly.
F. Assembly and use of chip carrier devices
Fig. 6A and 6B show perspective and cross-sectional views of a chip carried within an assembled chip carrier device 200 along the same cross-sectional view as shown in the various component cross-sectional views. It can be seen that each of the components of chip carrier device, fluid flow portion 210 and flow cell portion 220 of fluid sample adapter 201, and chip carrier 230 are engaged by one or more coupling features such that the fluid channels of fluid flow portion 210 are fluidly coupled to flow cell portion 220 for processing or analysis of a fluid sample by a semiconductor chip carried within the chip carrier adjacent to the flow cell. The electrical contacts 232 of the chip carrier 230 face outward for engagement with corresponding contacts of the instrument interface 300 to facilitate control of the semiconductor chip by the module, as described above.
Fig. 7A-7B show detailed views of chip-carrier device 200 assembled prior to coupling with sample cartridge 100. While these components of chip carrier device 200 are coupled and aligned by removable coupling features 229, it should be appreciated that such components may be coupled or permanently bonded by non-removable coupling features, such as by adhesive or heat sealing. It will also be appreciated that these components may be defined to receive the chip in various other ways, for example, they may be hinged or partially attached along one side. Alternatively, the fluid sample adapter and the chip carrier part may be formed as one integral part.
Fig. 8 shows a detailed view of sample cartridge 100 coupled with fluid sample adapter 201 via fluid interface 211 (other components of the chip carrier device are omitted for improved visibility). Fig. 9 shows an assembled chip carrier device 200 coupled to sample cartridge 100 through fluid interface 211 of fluid sample adapter 201. The end user may assemble the chip-carrier device and couple with the sample cartridge in this manner before placing the sample cartridge containing the fluid sample within the module for processing and analysis with the chip carried within the chip-carrier device 200.
Alternative example chip apparatus and related systems
A. Overview of the System
Fig. 10 illustrates a detailed view of sample cartridge 1100 fluidly coupled to chip-carrier device 1200 according to some embodiments. In this embodiment, chip-carrier device 1200 includes a fluid sample adapter 1210, a flow cell adapter 1220, and a chip carrier 1230. Fluid sample adapter 1210 is fluidly coupled to sample cartridge 1100 through a pair of fluid ports on the sample cartridge; flow cell adapter 1220 is fluidly coupled to fluid sample adapter 1210; and chip carrier 1230 is coupled to flow cell adapter 220 such that the chip carried in chip carrier 1230, along with flow cell adapter 1220, defines a flow cell. Any or all of the adapters or chip carriers of chip carrier device 1200 are formed of a suitably rigid material such that carrier device 1200 extends outwardly from sample cartridge 1100. In some embodiments, chip carrier device 200 is supported by only a pair of inlet studs of fluid sampling tube adapter 1210 that are properly received within a corresponding pair of fluid ports and surrounding flange of cartridge 1100.
B. Fluid sample adapter
Fig. 10-17 depict exemplary chip carrier device assemblies and components according to some embodiments. Such a device assembly may include a fluid sample adapter, a flow cell adapter, and a chip carrier component. As shown in fig. 11A, the fluid sample adapter 1210 includes two fluid channels or conduits that are spaced apart and extend within the chip carrier device. The channels are separated and supported by a support web structure. The chip carrier device may be made of any material suitable for delivering the selected fluid sample so as not to interfere with the processing or analysis of the sample, and generally inert plastic or polymer based materials may be used. In some embodiments, the components of the chip carrier device are formed of polycarbonate, polysulfone, or any suitable material (e.g., any material compatible with the adhesive). In some embodiments, the material may be compatible with silicone adhesives. In some embodiments, the material used to fabricate the chip carrier device is a transparent or partially translucent material to allow visual inspection of the sample transport and/or optical detection/monitoring of the fluid channel through the material.
In some embodiments, the chip carrier device includes a fluid sample adapter configured with the same luer port and flange arrangement of the fluid interface as a typical PCR reaction tube, so that the fluid sample adapter can be easily engaged with a sample cartridge. The fluid sample adapter is configured such that the port is fluidly coupled to the optional PCR pre-amplification chamber. Alternatively, the amplification chamber may house filters, affinity matrices, magnetic capture zones, or other active areas that can be manipulated by the module. Typically, a fluid channel is defined in a first substrate and sealed by a second substrate, such as a membrane, similar to the structure of a conventional PCR reaction tube. In some embodiments, the fluid sample adapter also has alignment and assembly bosses and mechanical snap features such that the flow cell adapter can be easily positioned and secured to the reaction tube adapter.
In some embodiments, the fluid sample adapter has a length of about 12cm, 11cm, 10cm, 9cm, 8cm, 7cm, 6cm, 5cm, 4cm, 3cm, 2cm, or 1cm. In some embodiments, the length of the fluid sample adapter 210 is between 3cm and 5cm, for example about 4cm, from the flange of the fluid interface 211, and the fluid channels extend in parallel and are spaced about 1cm apart. This configuration allows for a substantially fluid-tight coupling having substantially the same structure as a conventional reaction tube. The fluid-tight coupling of each channel is defined by a stub, each stub being sized to be received in a respective external port of the sample cartridge to facilitate fluid-tight coupling of the fluid channel with a respective fluid channel of the chip-carrier device. For example, the stubs along the fluid inlet and outlet 1212, 1214 at the proximal end of the chip-carrier device 1200 serve as inlet stubs for flowing the prepared fluid sample into the chip-carrier device 1200, while the stubs of the flow cell ports 1216', 1218' form a fluid-tight coupling for facilitating the flow of the prepared fluid sample into the flow cell chamber of the flow cell adapter. In some embodiments, the stubs may have an outer diameter of between 2mm and 10mm, for example, the outer diameter may be 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, or 10mm. Typically, the stub has an outer diameter of about 3mm and extends from the flange a distance of about 2mm-5mm, such as about 3mm, to facilitate fluid-tight coupling. In some embodiments, the inner diameter of each of the one or more channels within any component of the chip carrier device may be in the range of 1mm to 5 mm.
In some embodiments, the fluid sample adapter 1210 includes one or more channels extending between the fluid-tight couplings without any chambers, valves, or ports between the proximal and distal ends. In some embodiments, the fluid sample adapter 1210 includes one or more valves or ports. In some embodiments, the one or more channels may include one or more chambers or regions that may be used to process or analyze a fluid sample. For example, the fluid sample adapter may include one or more chambers or regions for thermal amplification of a nucleic acid target in a sample, filtration, sample, chromatographic separation, hybridization, and/or incubation of a sample with one or more assay reagents.
While the fluid-tight coupling shown in fig. 11A includes a stub extending from a flange of the fluid interface 1210, it should be appreciated that various other fluid-tight couplings suitable for fluid-coupling with other types of devices may be designed as desired. Non-limiting exemplary fluid-type couplings suitable for use with the present application include luer lock connections, snap fit connections, friction fittings, snap fit connections, and threaded connections. Other types of fluid tight couplings suitable for use in the present application are known to those skilled in the art.
As can be seen in fig. 11A-11B, the fluid sample adapter 1210 is defined by one or more planar substrates defining a fluid path 1213 coupled to the fluid interface 1211. Fluid interface 1211 is a structural member of a largely planar frame cantilever. The fluid interface 1211 may be integrally formed with a planar frame. Fluid interface 1211 also serves as a mechanical coupling to sample cartridge 100. Fluid interface 1211 includes a fluid inlet 1212 and a fluid outlet 1214, fluid outlet 1214 providing a fluid interface to a sample cartridge device. Each of the fluid inlet 1212 and the fluid outlet 1214 are fluidly coupled to a fluid path 1213 formed in the planar substrate.
In some embodiments, the fluid path 1213 is defined primarily along one major face of the planar substrate and is surrounded by a second planar substrate, such as a film heat sealed over the substrate, so as to enclose the channels and chambers defined within the substrate. The fluid path 1213 leads to a flow cell interface that includes a first set of flow cell ports 1216, 1218 extending generally perpendicularly transversely or transversely to the adapter plane for fluid coupling with the fluid path of the flow cell adapter (see fig. 12A-12C), which is coupled to the fluid sample adapter 1210 along a major face of the fluid sample adapter 1210. In this embodiment, the flow cell interface includes an inlet flow cell port 1216 and an outlet flow cell port 1218, the inlet flow cell port 1216 and the outlet flow cell port 1218 allowing for controlled fluid delivery into the flow cell chamber through the chip-carrier device 1200 via the fluid inlet 1212 and the fluid outlet 1214. In this embodiment, the fluid channel is defined along one major face of the fluid sample adapter 1210 and the flow cell adapter is coupled to the opposite major face. In such an embodiment, the first set of ports 1216 and 1218 are defined in the same major face in which the channels are formed, as shown in fig. 11B. The flow cell ports 1216, 1218 open into respective channels extending transversely through the adapter and opening along opposite major faces within respective protruding stubs 1216',1218', as seen in the cross-sectional views of fig. 11B and 11C. These protruding studs facilitate fluid-tight coupling with corresponding fluid ports in the flow cell adapter when coupled with the flow cell adapter. Although shown here as separate components, it is understood that the components of the chip carrier device may be formed as a unitary component. For example, the components shown in fig. 11A-12A may be formed as part of an integral component.
It should be understood that the use of the terms "inlet" and "outlet" does not limit the function of any of the fluid inlets or outlets described herein. Fluid may be introduced and removed from either or both. In some embodiments, the fluid path 1213 is valveless, such that an increase or decrease in external pressure may be applied by an external system via the fluid inlet 1212 and the fluid outlet 1214 to move fluid within the fluid path 1213, the fluid path 1213 extending from the fluid inlet 1212 to the fluid outlet 1214. The fluid path 1213 may be circular or rectangular in cross-section and may have a diameter or width ranging from about 50 μm to about 2 mm. Typically, the diameter or width is in the range of about 250 μm to about 1 mm. In this embodiment, the fluid path 1213 includes a chamber 1215, the chamber 1215 being an enlarged portion of the fluid path 1213 sized to accommodate most or all of the fluid sample delivered from the sample cartridge to facilitate various processes, including but not limited to flow metering, mixing, pre-amplification, thermal cycling, or any other desired sample processing. It will be appreciated that various other components may be incorporated into the fluid sample adapter, such as valves, filters, windows, or any other desired feature.
The fluid sample adapter 1210 also includes one or more coupling and/or alignment features. In this embodiment, the fluid sample adapter includes a coupling feature 1219, defined herein as a recessed region shaped for receipt, and a corresponding feature along the distal outboard edge of the flow cell adapter to couple the flow cell adapter thereto. Coupling feature 1219 may be defined to resiliently deflect to receive the flow cell adapter and secure the flow cell adapter when mounted within the recessed notch portion. In this embodiment, the fluid sample adapter further comprises an alignment feature 1219', which alignment feature 1219' fits into a corresponding alignment feature on the flow cell adapter, which alignment feature 1219' facilitates proper alignment and orientation of the flow cell adapter when the flow cell adapter is coupled thereto to ensure a fluid tight coupling between the corresponding fluid ports of the flow cell adapter and the first set of flow cell ports. In this embodiment, the alignment feature 119' is defined as a circular protrusion with a central aperture. It should be appreciated that various other coupling and alignment features (e.g., connection profile areas, snap-fit features, etc.) may be used, and that these features may be separate features or integrated into a single feature. In some embodiments, the fluid sample adapter and the flow cell adapter may be securely fastened together by heat sealing, adhesive, or any suitable means. In other embodiments, the fluid sample adapter and the flow cell adapter may be integrally formed as a single component.
In some embodiments, the chip-carrier device (or at least part of the assembly) is arranged to be pre-attached to the sample cartridge, wherein the fluid-tight coupling is coupled with a corresponding fluid port of the cartridge. For example, a sample cartridge that has been coupled with fluid sample adapter 1210 and attached to flow cell adapter may be provided so that an end user may insert any chip into chip carrier 1230 component and then couple to flow cell adapter 1220 within the chip carrier.
C. DC battery adapter
In some embodiments, the chip-carrier device includes a flow cell adapter configured with an open chamber that forms a closed flow cell chamber when docked with an active area of a chip within the chip-carrier to facilitate analysis of a fluid sample with the chip. In some embodiments, the flow cell is configured to be fluidly coupled to a fluid sample adapter and a chip within a chip carrier. Typically, the flow cell adaptor is connected to the flow cell chamber through fluid ports at the top and bottom of the chamber. The chamber is formed by raised bosses or ridges that contact the active silicon or glass elements used in the detection scheme. The active element is located on a chip carried within a chip carrier and secured to the flow cell by bonding and sealing, which may be accomplished by a variety of means (e.g., using an epoxy preform, dispensed epoxy or other adhesive, a gasket with adhesive, mechanical features, or a variety of other means). The purpose of the flow cell adapter is to create a complete flow cell chamber defined by the detection surface on one side and the flow cell dispenser on the remaining side. The flow cell adapter also has alignment and mounting bosses and mechanical snap features that allow the flow cell adapter to be easily positioned and secured to the fluid sample adapter.
Fig. 12A-12C illustrate detailed views of an exemplary flow cell adapter 1220 for use with the chip-carrier device 1200. In this embodiment, flow cell adapter 1220 is configured to be fluidly coupled to fluid sample adapter 1210 shown in fig. 11A. As shown in fig. 12A, flow cell adaptor 1220 is a planar substrate 1221 formed of a rigid material (e.g., a polymer or any suitable material) having a recessed portion 1222, an open flow cell chamber 1224, a channel 1225, and flow cell ports 1226, 1228 defined therein. Flow cell adapter 1220 is configured to couple with fluid sample adapter 1210 along one major face and with a chip along its opposite major face along the chip carrier. When the chip is engaged within the correspondingly shaped recess 1224, the opening chamber 1224 forms a closed flow cell chamber with the active area of the chip. A top flow cell port 1226 and a bottom flow cell port 1228 fluidly couple the flow cell chamber with the flow cell port set of the fluid sample adapter 1210 to allow fluid sample to flow into or out of the flow cell chamber when the inlet and outlet 1212, 1214 of the chip-carrier device 1200 fluidly coupled with the sample cartridge 1100 are controllably pressurized. The passage 1225 extends into the flow cell chamber and allows any of the following: entering the flow cell chamber, injecting material into the flow cell chamber, capturing any bubbles in the flow cell chamber, and pressure regulation.
As can be seen in the cross-sectional views in fig. 12B and 12C, each of the fluid ports 1226 and 1228 extends to an opposite major face of the flow cell adapter 1220 and opens into a recess or cavity of the boss 1226', 1228' to form a fluid-tight coupling with a port in a corresponding cylindrical protrusion or stub of the fluid sample adapter. It is understood that various other fluid tight couplings may be used to fluidly couple flow cell adapter 1220 to fluid sample adapter 1210.
Flow cell adapter 1220 further includes one or more coupling features and/or alignment features. In this embodiment, the flow cell adapter includes a coupling feature 1229, defined herein as a tab region shaped to be resiliently received within a corresponding recess region 1219 of the fluid sample adapter 1210. The flow cell adapter includes a ridge 1229' along each side edge that engages a corresponding feature (e.g., groove, ridge, etc.) of the fluid sample adapter to further assist in alignment and coupling of the adapters. In this embodiment, the flow cell adapter further comprises an alignment feature 1229a that mates into a corresponding feature on the fluid sample adapter to ensure proper alignment and orientation of the flow cell adapter when the flow cell adapter is coupled to the fluid sample adapter, thereby ensuring fluid-tight coupling between the corresponding fluid ports of the flow cell adapter and the first set of ports. In this embodiment, the alignment features 1229a are each defined as a rounded protrusion that fits into a corresponding alignment hole 1219a of the fluid sample adapter 1210. It should be appreciated that various other coupling and alignment features (e.g., connection profile areas, snap-fit features) may be used, and that these features may be separate features or integrated into a single feature. In some embodiments, the fluid sample adapter and the flow cell adapter may be securely fastened together by heat sealing, adhesive, or any suitable means. In some embodiments, the fluid sample adapter and the flow cell adapter may be integrated into a single component.
D. Chip carrier
Fig. 13A-13C illustrate detailed views of a chip carrier 1230 of a chip carrier device according to some embodiments. As can be seen in fig. 13A, the chip carrier 1230 is defined within a substantially planar substrate 1231, the substrate 1231 including a contoured region 1236, the contoured region 1236 being sized to accommodate a chip and configured to have a plurality of electrical contacts 1234, the electrical contacts 1234 being arranged to electrically couple with corresponding contacts of the chip when accommodating the chip. In this embodiment, the contoured region 1236 is square and the electrical contacts 1234 are configured to receive and couple with a chip, as shown in fig. 13A. Contoured region 1236 includes a ridge along its perimeter to engage a corresponding portion of the flow cell adapter and effectively seal the chip within the chip carrier device. The raised boss or ridge surrounding the open flow cell chamber engages the active surface of the chip to form a closed flow cell chamber, as described above.
The electrical contacts 123 are electrically coupled to corresponding contact arrays 1232 of an electrical interface board disposed on an opposite side of the chip carrier 1230, as shown in fig. 13B. Contact array 1232 is defined as an array of augmented contact pads arranged to facilitate contact with corresponding electrical contacts (typically pogo pins) of the module's instrument interface 1300. Fig. 13C shows a cross-sectional view of chip carrier 1230, wherein the chip is carried and electrically coupled within socket 1236. Wire bonding is not shown in this view. In addition to the electronic components of the chip carrier, the electrical interface board may also house passive and active electronic components as required by various other tasks. For example, such components may include any components required for signal integrity, amplification, multiplexing, or other such tasks.
E. Chip
In some embodiments, if chip 1240 includes a silicon sensor element, it may be bonded within chip carrier 1230 and wire bonds applied to electrically couple the silicon element to chip carrier 1230. In other embodiments, the chip may simply be pressed into the recess such that the friction fit provides sufficient electrical contact between the respective contacts.
In some embodiments, chip 1240 is a semiconductor diagnostic chip, such as any of those described herein. While semiconductor diagnostic chips are preferred, it should be understood that the concepts described herein are applicable to any type of chip suitable for performing processing or analysis of fluid samples.
It is understood that the chip-carrier device may be configured for use with any type of chip, including but not limited to CMOS chips, ISFET chips, bulk acoustic chips, non-bulk acoustic chips, piezoelectric acoustic chips, and aperture array sensor chips. In addition, the chip may be adapted for use in any of a number of JDEC standards used in open packages, including but not limited to QFN, dual in-line (dual in-line), and BGA arrays. Alternatively, the chip may be mounted directly to the PCB as a chip-on-board component.
F. Assembly and use of chip carrier devices
Fig. 14A and 14B illustrate cross-sectional views of an assembled chip carrier device 200 taken along the same cross-section as shown in the cross-sectional views of the various components. It can be seen that each of the chip set, fluid sample adapter 1210, flow cell adapter 1220 and chip carrier 1230 can be engaged by one or more coupling features such that the fluid channels of fluid sample adapter 1210 align with and fluidly couple to the flow cells of flow cell adapter 1220 to facilitate processing or analysis of a fluid sample with a semiconductor chip carried within the chip carrier adjacent to the flow cells. The electrical contacts 1232 of the chip carrier 1230 face outward for engagement with corresponding contacts of the instrument interface 1300 to facilitate control of the semiconductor chip with the module, as described above.
Fig. 14A and 14B illustrate detailed views of a chip carrier interface 1230 fluidly coupled to a flow cell adapter 1220. Fig. 15A and 15B show detailed views of a fully assembled chip carrier device 200 prior to fluid coupling with sample cartridge 100, and fig. 15C shows a cross-sectional view of the device. As shown, the device is configured such that semiconductor chips 1240 within carrier 1230 are exposed to the flow cell of flow cell adapter 1220. While these components are coupled and aligned by removable coupling features to allow an end user to assemble any chip within the device, it should be understood that these components may be coupled or permanently bonded by non-removable coupling features, such as by adhesive or heat sealing. It will also be appreciated that these components may be defined to house the chip in various other ways, e.g., they may be hinged or partially connected along one side. Fig. 15A and 15B show detailed views of chip-carrier device 200 prior to fluid coupling with sample cartridge 100, and fig. 15C shows a cross-sectional view.
Fig. 16 shows a detailed view of a sample cartridge coupled with fluid sample adapter 1210, fluid sample adapter 1210 being fluidly attached to sample cartridge 1100 through fluid interface 1211 (other components of the chip carrier device are omitted for improved visibility). Fig. 17 shows a fluid sample adapter 1210 coupled to flow cell adapter 1220 and chip carrier 1230 within entire chip-carrier device 1200, as well as to chips (not shown) carried within chip carrier 1230. The end user may assemble the chip carrier device and couple with the sample cartridge in this manner before placing the sample cartridge containing the fluid sample within the module for processing and analysis.
Fig. 18 illustrates an alternative detection mode configured for use with a sample cartridge according to some embodiments. Embodiment 0 depicts a sample cartridge 100 fluidly coupled to a reaction tube 110. Embodiment 1 depicts a sample cartridge 100 fluidly coupled to a fluid bridge 120, the fluid bridge 120 being adapted to facilitate the transport of a fluid sample to an external device for further processing or analysis. Embodiment 2 depicts a sample cartridge 100 that is fluidically coupled to a chip carrier device 200 carrying a semiconductor test chip, as described herein. Embodiment 3 describes an alternative structure of a chip-carrier device 200' carrying a semiconductor test chip according to the concepts described herein. In this embodiment, certain components of the chip carrier device have been eliminated by utilizing chip-on-board and epoxy preform structures or vertical interconnect vias such as bare through silicon vias ("TSVs") or glass integrated into the molded carrier tube. This design reduces the number of parts, thereby reducing the complexity and cost of the chip carrier device to allow for a mass production method to be performed. In addition, this design concept allows for plug and play methods, allowing the system to be used on a platform to easily accept and utilize existing "lab-on-a-chip" devices in a more cost effective manner. While in these embodiments the chip-carrier device is configured to carry the detection chip in a vertical direction, it should be understood that various other configurations and orientations may be utilized. In some embodiments, a chip-carrier device that utilizes a vertically oriented detection chip is advantageous because it further reduces the overall chip-carrier device size for fitting within a conventional sample processing module modified with an instrument interface for analysis utilizing chip control.
Sample processing method using chip carrier
Fig. 19-20 illustrate an exemplary method of processing a fluid sample through a semiconductor chip using a chip carrier device and a sample cartridge according to some embodiments.
Fig. 19 shows a method comprising the steps of: a sample cartridge containing a fluid sample therein is received within a container of a sample processing module. Such a module may be a module as described herein or any such module or similar module known in the art capable of receiving and processing a sample cartridge as described herein. The method further comprises the steps of: the module is utilized to perform one or more sample processing steps on the fluid sample within the sample cartridge and to transfer the processed fluid sample from the sample cartridge to a chip carrier device that is fluidly coupled to the sample cartridge. The delivery of the processed fluid sample may be performed by controlling the pressurization through a fluid port of the sample cartridge through which the carrier device is attached. The method further comprises the steps of: the processed fluid sample is analyzed by a semiconductor chip carried in a chip carrier device using a module. In some embodiments, the diagnostic result of the fluid sample analyzed using the chip is received by the module or determined by the module through the instrument interface.
Fig. 20 shows a method comprising the steps of: a chip carrier device is provided having a fluid sample adapter, a flow cell and a chip carrier carrying a semiconductor chip. As will be appreciated by those skilled in the art, such components may be as described above, or may include various modifications or additional adapters. The method may further comprise: the chip carrier device is fluidly coupled to a sample cartridge containing a fluid sample and the sample cartridge is placed into the processing module and the processed fluid sample is received from the sample cartridge within the fluid sample adapter of the chip carrier device through one or more fluid ports of the fluid sample adapter. The method may further comprise: the processed fluid sample is transferred from the fluid sample adapter to the flow cell of the chip carrier device through the first set of flow cell ports. In some embodiments, the chip-carrier device is valveless such that receiving and delivering a fluid sample through the chip-carrier device is performed by controlled pressurization of one or more fluid ports of a sample cartridge fluidly coupled to the chip-carrier device. The method may further comprise: the processed fluid sample in the flow cell is analyzed using a diagnostic semiconductor chip carried in a chip carrier of the chip carrier device.
As previously described, in one aspect, the adapter allows for bonding with chips that are not within conventional chip packages (e.g., chips mounted within leadframe wirebonds, packaged in epoxy), thereby providing improved ease of use and assembly as compared to conventional approaches, further reducing size and integration. In some embodiments, the chip-carrier device may include a standard set of open-ended chip carriers in which chips may be packaged. In other embodiments, the device may include a chip-on-board package that allows the chip to be inserted and engaged with the flow cell, as described above.
In the foregoing specification, the present application has been described with reference to specific embodiments thereof, but those skilled in the art will recognize that the present application is not limited thereto. The various features, embodiments and aspects of the above-described invention may be used alone or in combination. In addition, the present application may be used in any number of environments and applications other than those described herein without departing from the broader spirit and scope of the specification. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense. It will be appreciated that the terms "comprising," "including," and "having," as used herein, are intended to be interpreted as open-ended terms in the art, in particular.
Claims (42)
1. A fluid sample adapter comprising:
a planar frame defining a fluid path between the first planar substrate and the second planar substrate;
a fluid interface at one end of the planar frame, the fluid interface comprising a fluid inlet and a fluid outlet of the fluid path; and
a flow cell interface configured to couple with a flow cell adapter, wherein the flow cell interface includes a first set of ports in fluid communication with the fluid path to facilitate flow of a fluid sample introduced into the fluid sample adapter from the fluid inlet into a flow cell.
2. The fluid sample adapter of claim 1, wherein the fluid path is sealed closed by a membrane seal.
3. The fluid sample adapter of claim 1, wherein the first set of ports comprises one or more ports.
4. The fluid sample adapter of claim 1, wherein the first set of ports comprises at least two ports.
5. The fluid sample adapter of claim 4, wherein the at least two ports are disposed along a vertical axis when the planar frame is oriented vertically and the fluid outlet is directly above the fluid inlet.
6. The fluid sample adapter of claim 1, wherein the fluid inlet and the fluid outlet are oriented to open in a first direction within a plane of the planar frame, and the first set of ports are oriented to open in a second direction along a transverse plane.
7. The fluid sample adapter of claim 6, wherein the transverse plane is substantially perpendicular to a plane of the planar frame.
8. The fluid sample adapter of claim 6, wherein the first set of ports is disposed along a first major side of the planar frame, the flow cell being coupled along the first major side.
9. The fluid sample adapter of claim 1, wherein the first set of ports are arranged to align with respective one or more ports of the flow cell adapter when the fluid sample adapter is coupled to the flow cell adapter.
10. The fluid sample adapter of claim 9, further comprising:
an alignment feature facilitates aligning the first set of ports with the one or more ports of the flow cell adapter when the flow cell adapter is coupled to the fluid sample adapter.
11. The fluid sample adapter of claim 10, wherein the alignment feature comprises one or more of a mechanical boss or protrusion that engages with a corresponding hole or recess in the flow cell adapter.
12. The fluid sample adapter of claim 9, further comprising:
a coupling feature for facilitating coupling of the flow cell adapter to the fluid sample adapter when aligned, thereby fluidly sealing the first set of ports from the one or more ports of the flow cell adapter.
13. The fluid sample adapter of claim 12, wherein the coupling feature comprises a mechanical snap, an interface slot or contoured surface, or any combination thereof.
14. The fluid sample adapter of claim 1, further comprising:
a flow cell chamber defined within the planar frame; and
one or more flow cell ports in fluid communication with the flow cell chamber, the one or more flow cell ports in fluid communication with a first set of ports in the fluid sample adapter when coupled to the fluid sample adapter.
15. A flow cell adapter comprising:
A planar frame configured to couple with a fluid sample adapter;
a flow cell chamber defined within the planar frame; and
one or more flow cell ports in fluid communication with the flow cell chamber, the one or more flow cell ports configured to sealingly couple with a first set of ports in the fluid sample adapter when coupled with the fluid sample adapter.
16. The flow cell adapter of claim 15, further comprising:
an alignment feature for facilitating alignment of the one or more flow cell ports with the first set of ports of the fluid sample adapter when the one or more flow cell ports are coupled to the fluid sample adapter.
17. The flow cell adapter of claim 16, wherein the alignment feature comprises one or more of a mechanical boss or a protrusion that engages with a corresponding hole or groove in the flow cell adapter.
18. The flow cell adapter of claim 15, further comprising:
a coupling feature for facilitating coupling of the flow cell adapter to the fluid sample adapter when aligned, thereby fluidly sealing the first set of ports from the one or more ports of the flow cell adapter.
19. The flow cell adapter of claim 18, wherein the coupling feature comprises a mechanical snap, an interface slot or contoured surface, or any combination thereof.
20. The flow cell adapter of claim 15, wherein the planar frame is configured to couple with the fluid sample adapter on a first major side of the planar frame, the one or more flow cell ports disposed along the first major side of the planar frame.
21. The flow cell adapter of claim 20, wherein the flow cell chamber is defined along a second major side of the planar frame opposite the first major side.
22. The flow cell adapter of claim 21, wherein the flow cell chamber is defined by a raised portion on the second major side, the raised portion being defined to contact an active element used in a detection scheme.
23. The flow cell adapter of claim 22, wherein the planar frame includes coupling features and/or alignment features to couple the active elements in an aligned manner to form a flow cell between the second major side of the planar frame and the active elements.
24. The flow cell adapter of claim 23, wherein the coupling feature and/or the alignment feature is configured to couple and/or align a chip carrier supporting the active element.
25. The flow cell adapter of claim 24, wherein the coupling feature and/or the alignment feature comprises a mechanical boss or protrusion, a mechanical snap, an interface slot or contoured surface, or any combination thereof.
26. A chip carrier, comprising:
a planar frame capable of coupling with the flow cell portion of the fluid adapter;
an open carrier portion configured to receive and support a chip; and
an electrical interface having a plurality of electrical contacts electrically coupled to the open carrier portion for electrically coupling with the electrical contacts of the chip when the chip is carried within the carrier portion.
27. The chip carrier of claim 26, wherein the open carrier portion is configured to receive a chip.
28. The chip carrier of claim 26, wherein the open carrier portion is configured to support the chip in a vertical orientation.
29. The chip carrier of claim 26, wherein the open carrier portion is configured to receive any one of the following types of chips: CMOS chips, ISFET chips, bulk acoustic chips, non-bulk acoustic chips, piezoelectric acoustic chips, and aperture array sensor chips.
30. The chip carrier of claim 26, further comprising:
coupling features and/or alignment features for securely coupling the first major side of the planar frame to a planar surface of a flow cell adapter that at least partially defines a flow cell chamber therein such that the flow cell chamber is defined between the flow cell adapter and the active element when the chip carrier carries an active element and is coupled to the flow cell adapter.
31. The chip carrier of claim 26, wherein the open carrier portion is disposed on the first major side of the planar frame.
32. The chip carrier of claim 31, wherein the plurality of electrical contacts are disposed along a second major side of the planar frame opposite the first major side.
33. The chip carrier of claim 31, wherein the plurality of electrical contacts are arranged to engage corresponding contacts of a chip control board of a module when the chip carrier is coupled within a chip carrier device and is fluidly coupled with a sample processing cartridge operably coupled within the module.
34. The chip carrier of claim 26, wherein the electrical interface comprises one or more active components configured for signal integrity, amplification, multiplexing, or any combination thereof.
35. A module for performing sample processing, the module comprising:
a cartridge receiver adapted to receive and removably couple with a sample cartridge configured to hold an unprepared sample, the sample cartridge comprising a plurality of process chambers fluidly interconnected by one or more mechanisms, wherein the cartridge receiver comprises:
a cartridge interface unit configured to move the valve body to alter the fluidic interconnection between the plurality of sample processing chambers;
a pressure interface unit for applying pressure according to the position of the valve body to move fluid between the plurality of sample processing chambers,
a sample preparation controller configured to be in electronic communication with the assay processing device and configured to control the cartridge interface unit and the pressure interface unit to process an unprepared sample into a prepared sample within the sample cartridge; and
a chip control unit component having an instrument interface with a plurality of contacts arranged to engage with contacts of an electrical interface of a chip carrier device fluidly coupled to the sample cartridge when the sample cartridge is received within the cartridge receiver so as to analyze the sample using a chip carried within the chip carrier device.
36. The module of claim 35, wherein the chip control unit comprises one or more active components configured for signal integrity, amplification, multiplexing, or any combination thereof.
37. The module of claim 35, wherein the module further comprises:
a processor unit configured to perform analysis of a fluid sample exposed to active elements of the chip supported in the chip carrier device via the plurality of contacts of the instrument interface.
38. A method for processing a sample, the method comprising:
receiving a sample cartridge at a cartridge receiver of a module, the sample cartridge comprising a plurality of process chambers fluidically interconnected by one or more mechanisms;
receiving electronic instructions from a process control unit of the cartridge receiver to process an unprepared sample into a prepared sample;
performing a sample preparation method to process an unprepared sample into a prepared sample;
moving the prepared sample fluid into a chip carrier device that is fluidly coupled to the sample cartridge; and
analysis of the fluid sample is performed by a process control unit of the cartridge receiver electrically coupled to the chip using active elements of the chip supported within the chip carrier device.
39. The method of claim 38, wherein performing sample preparation comprises:
moving a cartridge interface unit to move a valve body of the sample cartridge to change fluidic interconnections between a plurality of sample processing chambers of the sample cartridge; and
pressure is applied to the pressure interface unit to move fluid between the plurality of process chambers according to the position of the valve body.
40. The method of claim 38, wherein the analysis of the fluid sample is performed within a flow cell of the chip-carrier device and is controlled by the processing unit through a plurality of contacts of an electrical interface of the chip-carrier device.
41. The method of claim 38, further comprising:
a leadless chip having the active element is coupled within a carrier portion of the chip carrier apparatus, wherein the leadless chip is configured to analyze a fluid sample with the active element.
42. The method of claim 41, wherein coupled within the chip-carrier device, the leadless chip comprises:
coupling the chip within a chip carrier adapter having the carrier portion and an electrical interface having a plurality of electrical contacts;
Coupling the chip carrier with a flow cell adapter that defines a flow cell chamber between the flow cell adapter and the active element of the chip when the chip is coupled to the flow cell adapter; and
the flow cell adapter is coupled to a fluid sample adapter having a fluid interface configured to be fluidly coupled with the sample processing cartridge to facilitate flow of the fluid sample therein for analysis using active elements of the chip within the chip carrier device.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862734079P | 2018-09-20 | 2018-09-20 | |
| US62/734,079 | 2018-09-20 | ||
| CN201980076476.4A CN113164951B (en) | 2018-09-20 | 2019-09-20 | Sample processing system, apparatus and method using semiconductor detection chip |
| PCT/US2019/052254 WO2020061515A1 (en) | 2018-09-20 | 2019-09-20 | System, device and methods of sample processing using semiconductor detection chips |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980076476.4A Division CN113164951B (en) | 2018-09-20 | 2019-09-20 | Sample processing system, apparatus and method using semiconductor detection chip |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117286021A true CN117286021A (en) | 2023-12-26 |
Family
ID=68165712
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980076476.4A Active CN113164951B (en) | 2018-09-20 | 2019-09-20 | Sample processing system, apparatus and method using semiconductor detection chip |
| CN202311029375.6A Pending CN117286021A (en) | 2018-09-20 | 2019-09-20 | Sample processing system, apparatus and method using semiconductor detection chip |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201980076476.4A Active CN113164951B (en) | 2018-09-20 | 2019-09-20 | Sample processing system, apparatus and method using semiconductor detection chip |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US11740256B2 (en) |
| EP (1) | EP3852927A1 (en) |
| KR (1) | KR20210093860A (en) |
| CN (2) | CN113164951B (en) |
| AU (2) | AU2019344001B2 (en) |
| CA (1) | CA3113526A1 (en) |
| WO (1) | WO2020061515A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB202015911D0 (en) * | 2020-10-07 | 2020-11-18 | Sigenex Inc | Systems and methods for processing a sample |
| CN114733587B (en) * | 2022-04-01 | 2024-02-20 | 合肥诺迈基生物科技有限公司 | Fluorescence detection chip, fluorescence detection system, fluorescence detection method and application thereof |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5856174A (en) | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
| US6220870B1 (en) * | 1998-02-27 | 2001-04-24 | Cerprobe Corporation | IC chip socket and method |
| US6818185B1 (en) * | 1999-05-28 | 2004-11-16 | Cepheid | Cartridge for conducting a chemical reaction |
| US8623379B2 (en) * | 2000-03-02 | 2014-01-07 | Emory University | Compositions and methods for generating an immune response |
| US8048386B2 (en) | 2002-02-25 | 2011-11-01 | Cepheid | Fluid processing and control |
| US6374684B1 (en) * | 2000-08-25 | 2002-04-23 | Cepheid | Fluid control and processing system |
| EP1226863B1 (en) * | 2000-12-28 | 2004-11-03 | F.Hoffmann-La Roche Ag | Method for processing a nucleic acid sample by swinging a segment of a cartridge wall, a system and a cartridge for performing such a method |
| JP4057967B2 (en) | 2002-07-31 | 2008-03-05 | 株式会社東芝 | Automatic nucleotide sequence analyzer |
| ITTO20020808A1 (en) * | 2002-09-17 | 2004-03-18 | St Microelectronics Srl | INTEGRATED DNA ANALYSIS DEVICE. |
| US20040086872A1 (en) * | 2002-10-31 | 2004-05-06 | Childers Winthrop D. | Microfluidic system for analysis of nucleic acids |
| WO2010117470A2 (en) | 2009-04-10 | 2010-10-14 | Pacific Biosciences Of California, Inc. | Nanopore sequencing devices and methods |
| DE102010002990A1 (en) | 2010-03-18 | 2011-09-22 | Robert Bosch Gmbh | Microfluidic system for analysis and diagnostic purposes and corresponding method for the production of a microfluidic system |
| US8444835B2 (en) * | 2010-09-09 | 2013-05-21 | Intel Corporation | Electronic and fluidic interface |
| US10161007B2 (en) | 2012-08-13 | 2018-12-25 | The Regents Of The University Of California | Methods and systems for detecting biological components |
| KR101504898B1 (en) | 2013-08-12 | 2015-03-23 | 앰코 테크놀로지 코리아 주식회사 | Micro-fluidic package |
| CA3077811C (en) * | 2015-03-24 | 2024-02-27 | Illumina, Inc. | Methods, carrier assemblies, and systems for imaging samples for biological or chemical analysis |
| EP3278116B1 (en) | 2015-04-02 | 2023-06-14 | Cepheid | Fluidic bridge device |
| ES2843532T3 (en) | 2015-07-23 | 2021-07-19 | Cepheid | Thermal control device and methods of use |
| JP7062587B2 (en) | 2015-07-24 | 2022-05-06 | セフェィド | Molecular diagnostic assay system |
-
2019
- 2019-09-20 CA CA3113526A patent/CA3113526A1/en active Pending
- 2019-09-20 US US16/577,650 patent/US11740256B2/en active Active
- 2019-09-20 AU AU2019344001A patent/AU2019344001B2/en active Active
- 2019-09-20 KR KR1020217011617A patent/KR20210093860A/en unknown
- 2019-09-20 CN CN201980076476.4A patent/CN113164951B/en active Active
- 2019-09-20 CN CN202311029375.6A patent/CN117286021A/en active Pending
- 2019-09-20 WO PCT/US2019/052254 patent/WO2020061515A1/en unknown
- 2019-09-20 EP EP19783771.9A patent/EP3852927A1/en active Pending
-
2023
- 2023-07-25 US US18/358,583 patent/US20240027487A1/en active Pending
-
2024
- 2024-02-15 AU AU2024200973A patent/AU2024200973A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20240027487A1 (en) | 2024-01-25 |
| AU2019344001B2 (en) | 2023-11-16 |
| CA3113526A1 (en) | 2020-03-26 |
| CN113164951A (en) | 2021-07-23 |
| CN113164951B (en) | 2023-09-08 |
| KR20210093860A (en) | 2021-07-28 |
| US11740256B2 (en) | 2023-08-29 |
| AU2024200973A1 (en) | 2024-03-07 |
| AU2019344001A1 (en) | 2021-05-20 |
| EP3852927A1 (en) | 2021-07-28 |
| US20200116750A1 (en) | 2020-04-16 |
| WO2020061515A1 (en) | 2020-03-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6664104B2 (en) | Device incorporating a microfluidic chip for separating analyte from a sample | |
| US6440725B1 (en) | Integrated fluid manipulation cartridge | |
| US8592157B2 (en) | Method for separating an analyte from a sample | |
| US20240027487A1 (en) | System, device and methods of sample processing using semiconductor detection chips | |
| US20060051248A1 (en) | Microfluidic bio sample processing apparatus capable of being assembled | |
| US20180031592A1 (en) | Fluidic bridge device and sample processing methods | |
| CN116273223A (en) | Diagnostic test chip device and method of manufacture and assembly | |
| AU764060B2 (en) | Integrated fluid manipulation cartridge |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |